The role of adrenergic receptor on obesity, how the story started and where we are now?

Its just this morning, I sit down and read some old publications made group of scientist from University of Limburg, now Maastricht University. In 90’s they published some interesting works about the role of adrenergic receptors. Surprisingly this study is still on going and new approaches are used.

In 1993, Blaak was studying the role of alpha and beta adrenergic receptor (AR) on thermogenesis. Using healthy male subject they infused beta AR agonist and the effect on those agonist on energy expenditure at rest using open circuit ventilated hood system. In the study, they did reveal that beta1 and beta2 AR is related to sympathetically mediated thermogenesis. This conclusion is made after observation that giving salbutamol (agonist of beta2AR) could increase energy expenditure significantly.

At the following year, a study was conducted. They were working on the role of those receptors on obese individual. This is interesting since the other study shown that SNS signal is impaired in obese individuals. In the study they investigated the effect of energy restriction on acute adrenoreceptor and metabolic responses to exercise in obese subjects. About 7 healthy female were assigned for a low energy diet within 4 weeks. After the diet, subjects have to do an exercise using bicycle ergometer. They did analyze the response of beta2 adrenoreceptor in lympocyte.

First, they found that 4 weeks dietary restriction did not change the density of beta2AR in lymphocyte. However the density increased as the response of diet. This effect did not seen in subjects before diet, meaning that the weight loss could be able to improve beta2AR density as the response of exercise. However, they also found that energy expenditure is decreased after 4 weeks of diet, but only resting energy expenditure no energy expenditure during training. This lead to assumption that weight loss induced decreased thermogenesis in resting but not during exercise. The other significant finding is that during weight loss, obese individuals are more likely to produce more glycerol and fatty acid thus reduce the usage of glucose. Seems like metabolism is shifted from glucose metabolism into fatty acid metabolism.

So, we have already know that beta2AR already induce thermogenesis and its function improved when obese people reduce weight. Its already known that the response of thermogenesis in obese subjects impaired. So how do we know that beta2AR is under this mechanism?

In 2001 Schiffelers et al published the data showing that beta2AR response is impaired in obese individuals. This finding suggested that thermogenesis and lipid utilization respons of beta2AR in obese subjects are not as good as in lean subjects. This study was done by giving salbutamol (a beta2AR agonist) to obese and lean men then see the effect on energy expenditure, lipid oxidation, respiratori exchange ratio and carbohydrate oxidation. In the study, obese men who induced with salbutamol have lower energy expenditure and lipid oxidation compared to lean men. However, carbohydrate oxidation and respiratory exchange ratio were higher in obese men. This study leads to conclusion that in obese people, the blunted of beta2AR response would make body use more carbohydrate instead of fat as energy source. This will have an effect on energy expenditure since the energy given by carbohydrate is two times lower than given by fat. This effect could also be related to insulin level of obese individual, in obese people the high insulin level would decrease lipolysis since insulin is the important anti-lipolytic agent.